# Protective immunity following dengue virus natural infections and vaccination

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $2,539,162

## Abstract

Mechanisms of Protective!Immunity after Dengue Natural Infections and Vaccination
OVERALL P01
SUMMARY
The four dengue virus serotypes (DENV1-4) cause the most important mosquito-borne viral disease of humans,
with 100 million cases annually. The mechanisms by which the host immune response to DENV provides either
protection against or enhancement of a subsequent infection with a different DENV serotype are not fully
understood, and this has been a major concern in vaccine development and implementation. The poor results
of the first registered dengue live attenuated vaccine highlight the critical need to better understand the immune
response to natural DENV infections and vaccine candidates and to identify robust correlates of protection. Our
current Program Project has been very successful, generating >50 high-level publications in 3.5 years and
producing key findings that are timely, topical, and impactful. Here, we propose to identify immune
mechanisms responsible for outcomes of DENV infection and vaccination, comprehensively exploring
both the antigenic specificity and Fc functionality of antibodies as well as the quality of T cell responses
in the context of long-term ongoing clinical and epidemiological studies of natural DENV infections and
vaccines. We integrate classical cutting-edge molecular genetic and systems serology approaches to
systematically examine both antigen specificity and Fc characteristics and effector functions of antibodies, as
well as T cell attributes, that predict protection or pathogenesis. We propose a coordinated P01 Program that
includes four projects: 1) Quality of B Cell and Antibody Responses to Natural Dengue Virus Infections; 2)
Dengue Vaccines: Linking Vaccine-Induced Antibody Responses to Protective or Disease-Enhancing Immunity;
3) Quality of T Cell Responses Following Dengue Virus Natural Infections and Live-Attenuated Dengue Virus
Vaccination, and 4) Genetic and Structural Basis for Human Antibody Inhibition of Dengue Viruses. The P01
is highly synergistic in that samples from the same individuals, as well as specific assays, reagents and
methodologies, are shared among the Projects, which are supported by an Administrative Core, Computational
Biology and Statistical Modeling Core, and Clinical and Data Management Core. We will leverage unique
sample sets from the longest continuous cohort study of dengue, in Nicaragua, as well as a cohort study
following recipients of the Dengvaxia® vaccine in the Philippines and human challenge studies of the NIH live
attenuated vaccine. We have have expanded our existing P01 Consortium of world-renowned investigators with
extensive experience and on-going programs in dengue clinical, immunological, and virological research and
vaccine development – thus ensuring a continued high-quality successful research program. All the partners
have a long-standing record of collaboration and numerous joint publications (>225). The Specific Aims
are: 1) Define the antigenic repe...

## Key facts

- **NIH application ID:** 10458124
- **Project number:** 5P01AI106695-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Eva Harris
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,539,162
- **Award type:** 5
- **Project period:** 2015-07-29 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458124

## Citation

> US National Institutes of Health, RePORTER application 10458124, Protective immunity following dengue virus natural infections and vaccination (5P01AI106695-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458124. Licensed CC0.

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